Fragilysin

Fragilysin is a zinc-dependent metalloprotease produced by the bacterium Bacteroides fragilis. It is a virulence factor that contributes to the pathogenicity of B. fragilis in intra-abdominal infections and sepsis.

Structure and Function

Fragilysin is a 20 kDa enzyme that belongs to the metalloprotease family. It is characterized by its dependence on zinc for its enzymatic activity. The enzyme cleaves extracellular matrix proteins such as collagen, fibronectin, and laminin, thereby disrupting the integrity of epithelial cell layers and facilitating bacterial invasion.

Role in Disease

B. fragilis is a commensal bacterium that is part of the normal gut flora. However, when it escapes the gastrointestinal tract due to trauma or surgery, it can cause serious infections. Fragilysin is a key virulence factor in these infections. It damages the endothelial cells lining the blood vessels, leading to increased vascular permeability and edema. This can result in sepsis and shock.

In addition to its role in acute infections, fragilysin may also contribute to chronic diseases. Studies have suggested that it can promote colorectal cancer by inducing DNA damage and inflammation in the colon.

Therapeutic Potential

Given its role in B. fragis infections, fragilysin is a potential target for antimicrobial therapy. Inhibitors of the enzyme could be used to reduce the virulence of the bacterium and prevent or treat infections. However, more research is needed to develop such inhibitors and assess their efficacy and safety.